MORAG PARK

Integrating Tumour-Microenvironment Biomarkers to Improve Diagnostic and Facilitate Targeted Breast Cancer Therapy

Challenge: It has become increasingly clear that breast cancer progression, response to therapy and ultimately disease outcomes are determined not only by features of the tumour itself, but also by characteristics of, and interactions with the surrounding tissue, or stroma. Currently, stromal information is not used for patient stratification in clinical setting, trial design or retrospective analyses of drug efficacy due to the lack of standardized tests suitable for assigning tumour samples to specific stromal subclasses.

Solution: The team has generated and validated distinct tumor microenvironment profiles. They have used TaqMan technology and gene expression profiling to establish mRNA and microRNA signatures of tumours and matched stroma obtained from 118 breast cancers patients with poor outcome. The team has demonstrated that incorporating stromal gene and miRNA expressions allows for a better stratification of patients than tumour gene expression alone. The identification of new tissue and blood biomarkers, which integrate the intrinsic and stromal characteristics of the tumor, allows for better stratification of patients with triple negative breast cancer (TNBC) with potential to predict responders to treatments.

Achievements/Impact: The team has developed a prognostic test integrating biomarkers from tumour environment to predict TNBC patient’s response to chemotherapy. These tools provide novel methods to stratify TNBC samples and to identify new patient subgroups. These profiles can now be applied to prospective stratification of patients in new trials as well as in retrospective analysis of material from previous trials where responder populations were small and could not be identified via existing companion diagnostics (thus the relevant drugs were considered as non-effective). These advances in multifactorial effect of stroma on disease outcome are improving the identification of patients who are unlikely to respond to current treatments but could benefit from personalized therapeutic strategies like immuno-oncology treatments, targeting specific disease configurations defined by intersections of tumour-intrinsic and stromal properties. A novel stratification scheme for triple-negative disease based on immune cell localization is currently under development.

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigator:


Morag Park
McGill University

Co-investigators

Michael Hallet,
Atilla Omeroglu

McGill University

Completed Project
$ 1,313,000 / 3 years
Supported by CQDM through:
• AstraZeneca
• Merck
• Pfizer
• MEI
• BL-NCE